Cyclooxygenase-2 and gastric carcinogenesis

Kirsi Saukkonen, Johanna Rintahaka, Anna Sivula, Christianne J. Buskens, Bastiaan P. van Rees, Marie-Christine Rio, Caj Haglund, J. Jan B. van Lanschot, G. Johan A. Offerhaus, Ari Ristimaki

Research output: Contribution to journalReview articleAcademicpeer-review

121 Citations (Scopus)

Abstract

Epidemiological studies have shown that the use of nonsteroid anti-inflammatory drugs (NSAIDs) is associated with reduced risk of gastric cancer. The best-known target of NSAIDs is the cyclooxygenase (Cox) enzyme. Two Cox genes have been cloned, of which Cox-2 has been connected with gastric carcinogenesis. Expression of Cox-2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis. This suggests that Cox-2-derived prostanoids promote aggressive behavior of adenocarcinomas of the stomach. Cox-2 expression is especially prominent in intestinal-type gastric carcinoma and it is already present in dysplastic precursor lesions of this disease, which suggests that Cox-2 contributes to gastric carcinogenesis already at the preinvasive stage. Our most recent data show that Cox-2 is expressed in gastric adenomas of trefoil factor 1 deficient mice. Treatment of these mice with a Cox-2 selective inhibitor, celecoxib, reduced the size of the adenomas. Taken together these data support efforts to initiate clinical studies to investigate the effect of Cox-2 inhibitors as chemotherapeutic agents and as adjuvant treatment modalities against gastric neoplasias
Original languageEnglish
Pages (from-to)915-925
JournalAPMIS
Volume111
Issue number10
DOIs
Publication statusPublished - 2003

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